Periodontitis is a chronic inflammatory disease affecting the tissues that surround and support the teeth. In the United States, approximately 65 million people are affected by this condition. Its occurrence is also associated with many important systemic diseases such as cardiovascular disease,rheumatoid arthritis, and Alzheimer?s disease. Among the most important etiologies of periodontitis is Porphyromonas gingivalis, a keystone bacterial pathogen. A keystone pathogen can orchestrate inflammatory disease by remodelling a normally benign microbiota causing imbalance between normal and pathogenic microbiota (dysbiosis). The important characteristics of P. gingivalis causing dysbiosis is its virulence characteristics that causes effective subversion of host defenses to its advantage, allowing other pathogens to grow. However, the mechanisms involving these processes are poorly understood. Polymorphonuclear leukocytes (neutrophils) represent the primary cellular defense system in healthy oral tissues, but recent studies indicate that neutrophils can be involved in the initiation and progression of periodontitis when their function is subverted by periodontal bacteria. To date, most studies on the subversion of neutrophils by P. gingivalis have focused on integrins and complement mediated processes. However, various microbial strategies target host sialoglycoproteins for immune dysregulation. In addition, sialoglycans (sialic acid attached with carbohydrate component) on bacterial surface structures as well as virulence factors can also facilitate immune evasion leading to dysbiosis. The enzymes that break down sialoglycoproteins / sialoglycans are the ?sialoglycoproteases?, resulting in exposed terminal sialic acid. This process could lead to pathogen-toll like receptor (TLR) interactions mediated through sialic acid receptor - ligand mechanisms. Such a mechanism in P. gingivalis, needs to be clarified. The P. gingivalis genome codes for two sialoglycoproteases (PG-Sgps) (PG0778 & PG1724) [21], however, there is significant gap in understanding how on how PG-Sgps are involved in sialoglycan modifications and play a role in virulence and host immune response. Our preliminary data suggests that PG-Sgps can modify major virulence factors in P. gingivalis, and modulate virulence. We have also found unique sialogycans on P. gingivalis that may be important for such interactions. The objectives of this study are (i) to explore the functional role of PG-Sgps in virulence modulation by identifying specific sialoglycan variations in two important virulence determinants of P. gingivalis, and (ii) to study how PG-Sgps interact with neutrophils and influence the pathogenic potential of P. gingivalis. Our long term goal is to understand the role of PG-Sgps in manipulating innate immunity through sialic acid ligand binding interactions and how these interactions lead to immune subversion and dysbiotic inflammation. This study will provide options for disease intervention by identifying the sialic acid interacting ligands as potential drugs targets.